与老年患者相比，年轻的非小细胞肺癌 (NSCLC) 患者（<50 岁）代表了一个重要的患者群体，具有独特的临床病理特征和丰富的靶向基因组改变。然而，之前针对年轻 NSCLC 的研究结果不一致，很少有研究将性别纳入分析，并且缺乏针对肿瘤免疫微环境中与年龄相关的差异的研究。我们对 8,230 名 NSCLC 患者进行了回顾性分析，比较了基因组改变和年轻和老年患者的免疫原性标志物，同时还考虑男性和女性患者之间的差异。我们将老年患者定义为≥65岁的患者，并使用从<45岁到<65岁的5年滑动阈值来定义各组年轻患者。此外，在一个独立的 NSCLC 患者队列中，我们利用我们的观察结果来测试年龄和性别对接受或不接受化疗的免疫治疗的患者生存的组合影响。我们观察到年轻患者肿瘤的不同基因组和免疫微环境特征与老年患者的肿瘤相比。年轻患者的肿瘤富含临床相关的基因组改变，并且具有表明免疫系统激活减少的基因表达模式，这在分析男性患者时最为明显。此外，我们发现，与≥65岁的男性患者相比，仅接受免疫治疗的年轻男性患者的生存率明显较差，而联合化疗则缩小了这种差异。相反，我们发现，与 ≥65 岁的女性患者相比，接受免疫治疗加化疗时，年轻女性患者的生存率明显更高，而单独使用免疫治疗的治疗结果相似。这些结果显示了综合基因组和免疫分析 (CGIP) 的价值为年轻 NSCLC 患者的临床治疗提供信息，并为更广泛的 CGIP 覆盖晚期 NSCLC 年轻患者提供支持。版权所有 © 2024 Wallen, Ko, Nesline, Hastings, Strickland, Previs, Zhuang, Pabla, Conroy, Jackson, Saini, Jensen,艾森伯格、卡夫尼、萨蒂安、塞弗森和拉姆基松。

Younger patients with non-small cell lung cancer (NSCLC) (<50 years) represent a significant patient population with distinct clinicopathological features and enriched targetable genomic alterations compared to older patients. However, previous studies of younger NSCLC suffer from inconsistent findings, few studies have incorporated sex into their analyses, and studies targeting age-related differences in the tumor immune microenvironment are lacking.We performed a retrospective analysis of 8,230 patients with NSCLC, comparing genomic alterations and immunogenic markers of younger and older patients while also considering differences between male and female patients. We defined older patients as those ≥65 years and used a 5-year sliding threshold from <45 to <65 years to define various groups of younger patients. Additionally, in an independent cohort of patients with NSCLC, we use our observations to inform testing of the combinatorial effect of age and sex on survival of patients given immunotherapy with or without chemotherapy.We observed distinct genomic and immune microenvironment profiles for tumors of younger patients compared to tumors of older patients. Younger patient tumors were enriched in clinically relevant genomic alterations and had gene expression patterns indicative of reduced immune system activation, which was most evident when analyzing male patients. Further, we found younger male patients treated with immunotherapy alone had significantly worse survival compared to male patients ≥65 years, while the addition of chemotherapy reduced this disparity. Contrarily, we found younger female patients had significantly better survival compared to female patients ≥65 years when treated with immunotherapy plus chemotherapy, while treatment with immunotherapy alone resulted in similar outcomes.These results show the value of comprehensive genomic and immune profiling (CGIP) for informing clinical treatment of younger patients with NSCLC and provides support for broader coverage of CGIP for younger patients with advanced NSCLC.Copyright © 2024 Wallen, Ko, Nesline, Hastings, Strickland, Previs, Zhang, Pabla, Conroy, Jackson, Saini, Jensen, Eisenberg, Caveney, Sathyan, Severson and Ramkissoon.